Differences in synovial tissue infiltrates between anti–cyclic citrullinated peptide–positive rheumatoid arthritis and anti–cyclic citrullinated peptide–negative rheumatoid arthritis

Oosterhout, M. van; Bajema, Ingeborg M.; Levarht, E. W. Nivine; Toes, René E. M.; Huizinga, Tom W J; Laar, Jacob M van

doi:10.1002/art.23148

Cited by 121 publications

(81 citation statements)

References 21 publications

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“…Synovial membranes from anti-CCP-positive RA patients demonstrated greater numbers of infi ltrating lymphocytes, including CD8-positive T cells, yet the membranes of anti-CCP-negative RA patients showed higher fi brosis scores, with a thicker synovial lining layer [ 14 ]. These distinct pictures are consistent with the presumed activation of self-reactive T cells in anti-CCP-positive patients.…”

mentioning

confidence: 65%

Anticyclic citrullinated peptide antibody-negative rheumatoid arthritis: Clues to disease pathogenesis

Crow

2008

Curr Rheumatol Rep

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mentioning

confidence: 65%

Anticyclic citrullinated peptide antibody-negative rheumatoid arthritis: Clues to disease pathogenesis

Crow

2008

Curr Rheumatol Rep

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“…Disappointingly, none of these features is pathognomonic for RA [6], nor do they help in distinguishing different clinical phases [24,25] or anti-citrullinated protein antibody (ACPA)-positive versus ACPA-negative disease phenotypes [26]. Within such stereotyped response (namely the presence of the same types of immune and stromal cells) implying qualitative homogeneity, virtually every histopathological marker shows high degrees of quantitative interpatient variability.…”

Section: Heterogeneity Of Individual Synovial Cell Populationsmentioning

confidence: 99%

Synovial Tissue Heterogeneity and Peripheral Blood Biomarkers

et al. 2011

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Rheumatoid arthritis is characterized by multiple pathobiological processes and heterogeneous clinical phenotypes. Not surprisingly, the inflamed synovium harbors an equally complex pathology. This includes variability in infiltrating and resident cell populations, spatial arrangements, and cell-cell interactions, as well as gene expression profiles. Remarkable progress in our understanding of the many facets of tissue heterogeneity has been facilitated by the increasing availability of patients' material and the development of advanced research technologies. The next challenge is to capitalize on the large amount of data generated to elucidate the specific pathogenic pathways disparately activated in different patients and/or different phases of the disease. When tissue pathology can be reliably explored through noninvasive circulating biomarkers, then the circle will be closed. We attempt to highlight key advances in the understanding of synovial tissue heterogeneity in rheumatoid arthritis and summarize novel perspectives in synovial biomarker discovery in relation to peripheral blood.

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“…Several facts show that both genetic and environmental risk factors for ACPA-positive and ACPA-negative RA are different, 17,19 as well as the clinical course, histology and response to therapy. 20,21 The aim of this study was to use three different relatively large case-control studies to investigate the potential interactions between HTR2A and HLA-DRB1 SE alleles in proving risk for RA, and to estimate where biological interaction may take place.…”

Section: Introductionmentioning

confidence: 99%

Evidence for interaction between 5-hydroxytryptamine (serotonin) receptor 2A and MHC type II molecules in the development of rheumatoid arthritis

et al. 2010

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It has repeatedly been suggested that the development of complex diseases can be elucidated by gene-gene interactions. Recently, we found that HTR2A, a member of the serotonin receptor family, is associated with rheumatoid arthritis (RA). This study was aimed to investigate the possibility of a gene-gene interaction between HTR2A and the major genetic risk factor for RA, HLA-DRB1 shared epitope (SE) alleles. We studied 4095 RA cases and 3223 controls from three different populationsfrom Sweden, the United States and the Netherlands -to test for interaction between the protective HTR2A haplotype and HLA-DRB1 SE alleles. Further, we analyzed mRNA and/or protein expression of HTR2A and HLA-DR in biopsy samples and in synovial fibroblasts from RA patients. The interaction was defined as departure from additivity of effects using attributable proportion due to interaction. First, we could demonstrate and further replicate an interaction between a protective haplotype in HTR2A and HLA-DRB1 SE alleles regarding risk of developing autoantibody-positive RA. Second, we could show that both genes are constitutively expressed in fibroblasts from synovial tissue of RA patients, and, by double immunofluorescence staining, we demonstrated that these two proteins are colocalized in these cells. In conclusion, our data demonstrate a statistical interaction between HTR2A and HLA-DRB1 SE alleles and colocalization of the product of these two genes in inflamed synovial tissue, which suggest a possible biological relationship between these two proteins. This finding may lead to the development of treatment based on enhancing the protective features of 5-HT2A in individuals with a certain HLA genotype.

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Differences in synovial tissue infiltrates between anti–cyclic citrullinated peptide–positive rheumatoid arthritis and anti–cyclic citrullinated peptide–negative rheumatoid arthritis

Cited by 121 publications

References 21 publications

Anticyclic citrullinated peptide antibody-negative rheumatoid arthritis: Clues to disease pathogenesis

Anticyclic citrullinated peptide antibody-negative rheumatoid arthritis: Clues to disease pathogenesis

Synovial Tissue Heterogeneity and Peripheral Blood Biomarkers

Evidence for interaction between 5-hydroxytryptamine (serotonin) receptor 2A and MHC type II molecules in the development of rheumatoid arthritis

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